Antimicrobial compositions

ABSTRACT

A method for rapid surface sanitization is provided, where the method includes contacting the surface with an effective amount of an antimicrobial composition comprising at least about 50 wt. % of a C 1-6  alcohol, based upon the total weight of the antimicrobial composition; and an efficacy-enhancing amount of a C 1-10  alkane diol.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Ser. No.61/187,041 filed on Jun. 15, 2009, which is incorporated herein byreference.

TECHNICAL FIELD

One or more embodiments of the present invention provide a method forsurface disinfection, where the method includes contacting the surfacewith an antimicrobial composition that includes an efficacy-enhancingamount of a C₁₋₁₀ alkane diol.

BACKGROUND OF THE INVENTION

There is a need in healthcare settings for efficacious broad-spectrumantimicrobial skin disinfection and hand wash products. Hand washingfrequently is called the single most important measure to reduce therisks of transmitting micro organisms from one person to another or fromone site to another on the same patient.

The United States Food and Drug Administration (FDA) developedperformance standards for new and novel antiseptic compositions. Theseperformance standards require a healthcare personnel hand wash to bebroad spectrum and fast acting. The term broad spectrum is defined inthis instance as having antimicrobial activity against a variety of grampositive and gram negative bacteria, and yeasts. The FDA set forthtesting procedures by which new antiseptics are tested alongsidepreviously approved products. Requirements for healthcare personnel handwash are outlined in the FDA Tentative Final Monograph for HealthcareAntiseptic Drug Products (TFM) (Federal Register 59 [116], Jun. 17,1994: pp. 31402-31452). The in vivo test procedure described beginningtherein will hereinafter be referred to as the FDA TFM healthcarepersonnel hand wash test. Testing procedures have also been set forth inthe TFM for surgical scrubs and pre-operative skin disinfectingproducts. A need continues to exist for healthcare personnel hand washproducts with efficacy that meets the Monograph requirements, as well asother standards such as European norms.

Certain diols such as 1,2-alkane diols have been used in cosmeticproducts as humectants or moisturizers, and have even been shown toexhibit preservative ability when present in certain cosmeticformulations.

However, preservatives are not expected to show rapid efficacy such asthat required for topical sanitizers and skin disinfecting compositions.Rather, preservatives exhibit their effects in 1 to 3 days or longer.That is, preservatives may be expected to inhibit microbial growth, butmay not be sufficiently lethal to produce significant log kill ofexisting microbes. Additionally, many preservatives show poor activityagainst fungi. A need continues to exist for broad-spectrumantimicrobial products with rapid efficacy.

Others who have employed alkane diols as a preservative include U.S.Published Patent Application No. 2007/0059331, which teachesantimicrobial mixtures comprising one or more branched or unbranchedalkane diols having 6-12 carbon atoms, and a tropolone. The mixtures areclaimed to have a synergistic antimicrobial activity, and may be used asa preservative or antimicrobial active compound in a foodstuff or acosmetic or a pharmaceutical formulation. Examples of formulationsinclude sunscreen lotions and silicone emulsions.

U.S. Published Patent Application No. 2005/0222276 teaches synergisticmixtures of 1,2-alkane diols for the preservation of perishableproducts. They can also be used for the cosmetic treatment ofmicroorganisms causing body odor, acne, mycoses, and for the treatmentof microorganism on or in inanimate material.

U.S. Published Patent Application No. 2005/0228032 teaches a blend of1,2-diol and phenoxyethanol and a co-biocide. The blend is suggested tocontrol microbiological growth in personal care products.

However, a need remains for compositions having rapid, broad spectrumefficiency such as required for health care personal handwash.

SUMMARY OF THE INVENTION

In one or more embodiments, the present invention provides a method forskin sanitization, the method comprising contacting the skin with aneffective amount of an antimicrobial composition comprising at leastabout 50 wt. % of a C₁₋₆ alcohol, based upon the total weight of theantimicrobial composition; and a C₆₋₁₀ alkane diol.

In one or more embodiments, the present invention provides a method forrapid surface sanitization, the method comprising contacting the surfacewith an effective amount of an antimicrobial composition comprising atleast about 50 wt. % of a C₁₋₆ alcohol, based upon the total weight ofthe antimicrobial composition; and an efficacy-enhancing amount of aC₆₋₁₀ alkane diol.

In one or more embodiments, the present invention provides a foamableantimicrobial composition comprising at least about 50 wt. % of a C₁₋₆alcohol, based upon the total weight of the antimicrobial composition; aC₆₋₁₀ alkane diol; and a foaming surfactant.

In one or more embodiments, the present invention provides anantimicrobial wipe composition comprising at least about 50 wt. % of aC₁₋₆ alcohol, based upon the total weight of the antimicrobialcomposition; and a C₆₋₁₀ alkane diol.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

In one or more embodiments, the present method provides an antimicrobialcomposition. The physical form of the antimicrobial composition is notparticularly limited, and in one or more embodiments, the compositionmay be presented as a liquid that is poured, pumped, sprayed, orotherwise dispensed, a gel, an aerosol, or a foam, including bothaerosol and non-aerosol foams. In addition to being effective as a handsanitizer, the antimicrobial composition of the present invention may beemployed on a wide variety of surfaces or substrates, including skin,porous, and non-porous surfaces. In one or more embodiments, theantimicrobial composition may be presented as a wipe, i.e. a tissue orcloth that is wiped over a surface.

The antimicrobial composition comprises a C₁₋₆ alcohol and an enhancer.In one embodiment, the alcohol is a lower alkanol, i.e. an alcoholcontaining 1 to 6 carbon atoms. Typically, these alcohols haveantimicrobial properties. Examples of lower alkanols include, but arenot limited to, methanol, ethanol, propanol, butanol, pentanol, hexanol,and isomers and mixtures thereof. In one embodiment, the alcoholcomprises ethanol, propanol, or butanol, or isomers or mixtures thereof.In another embodiment, the alcohol comprises ethanol.

Generally, the antimicrobial composition comprises at least about 30percent by weight (wt. %) alcohol, based upon the total weight of theantimicrobial composition. In one embodiment, the antimicrobialcomposition comprises at least about 50 weight percent alcohol, inanother embodiment, the antimicrobial composition comprises at leastabout 60 weight percent alcohol, in another embodiment, theantimicrobial composition comprises at least about 65 weight percentalcohol, in yet another embodiment, the antimicrobial compositioncomprises at least about 70 weight percent alcohol, and in still yetanother embodiment, the antimicrobial composition comprises at leastabout 78 weight percent alcohol, based upon the total weight ofantimicrobial composition. More or less alcohol may be required incertain instances, depending particularly on other ingredients and/orthe amounts thereof employed in the composition. In certain embodiments,the antimicrobial composition comprises from about 50 weight percent toabout 98 weight percent alcohol, in other embodiments, the antimicrobialcomposition comprises from about 60 weight percent to about 95 weightpercent of alcohol, in yet other embodiments, the antimicrobialcomposition comprises from about 65 weight percent to about 90 weightpercent of alcohol, and in still other embodiments, the antimicrobialcomposition comprises from about 70 weight percent to about 85 weightpercent of alcohol, based upon the total weight of the antimicrobialcomposition.

Rapid antimicrobial efficacy is observed at lower concentrations ofalcohol when an enhancer is present compared to when the enhancer is notpresent.

Advantageously, it has been found that antimicrobial compositionscomprising alcohol and an efficacy-enhancing amount of an enhanceraccording to the present invention have increased efficacy against abroad spectrum of gram positive and gram negative bacteria, fungi,parasites, and viruses, when compared to antimicrobial compositionscomprising alcohol without enhancer. In one or more embodiments, thediol comprises a straight chain diol. In one or more embodiments, theenhancer comprises one or more C₆₋₁₀ alkane diols, i.e. diols having acarbon chain length of 6 to 10. In one or more embodiments, the diolincludes 1,2-hexanediol, 1,2-octanediol, 1,9-nonanediol, 1,2-decanediol,1,10-decanediol, or a mixture thereof. 1,2-octanediol is sometimesreferred to as caprylyl glycol. 1,2-decanediol is sometimes referred toas decylene glycol. In one or more embodiments, the diol comprises oneor more C₆₋₈ alkane diols, i.e. diols having a carbon chain length of 6to 8.

In one embodiment, an efficacy-enhancing amount of diol is at leastabout 0.02 wt. %, based upon the total weight of the antimicrobialcomposition, in another embodiment at least about 0.05, and in yetanother embodiment at least about 0.1 wt. %, based upon the total weightof the antimicrobial composition.

Generally, an efficacy-enhancing amount of diol is from about 0.02 toabout 10 wt. %, based upon the total weight of the antimicrobialcomposition. In one embodiment, the diol is present in an amount of fromabout 0.05 to about 5 weight percent, in another embodiment, the diol ispresent in an amount of from about 0.1 to about 1 wt. %, in yet anotherembodiment, from about 0.15 to about 0.8 wt. %, and in still yet anotherembodiment, from about 0.2 to about 0.75 wt. %, based upon the totalweight of the antimicrobial composition. It will be understood thatgreater amounts of diol can be employed, if desired, and are expected toperform at least equally as well.

In certain embodiments, the diol is added to the antimicrobialcomposition as a solution or emulsion. In other words, the diol may bepremixed with a carrier to form a diol solution or emulsion, with theproviso that the carrier does not deleteriously affect the sanitizingproperties of the composition. Examples of carriers include water,alcohol, glycols such as propylene or ethylene glycol, ketones, linearand/or cyclic hydrocarbons, triglycerides, carbonates, silicones,alkenes, esters such as acetates, benzoates, fatty esters, glycerylesters, ethers, amides, polyethylene glycols and PEG/PPG copolymers,inorganic salt solutions such as saline, and mixtures thereof. It willbe understood that, when the diol is premixed to form a diol solution oremulsion, the amount of solution or emulsion that is added to theantimicrobial composition is selected so that the amount of diol fallswithin the ranges set forth hereinabove.

It is believed that, in one or more embodiments, the diol enhancesantimicrobial efficacy by retarding evaporation of the alcohol and/orother antimicrobial agent if present, thereby providing increasedcontact time.

It is believed that, in one or more embodiments, the diol lowers thewater activity of the alcoholic composition thus increasing the apparentalcohol concentration and thus increasing the antimicrobial activity ofthe alcoholic composition.

It is believed that, in one or more embodiments, the enhanced alcoholiccomposition maintains antimicrobial efficacy by killing or preventingthe growth or establishment of transient microorganisms.

In one or more embodiments, the antimicrobial composition is a foamablealcoholic composition. Foamable antimicrobial alcoholic compositions inaccordance with this invention include at least one alcohol, an C₁₋₁₀alkane diol enhancer, and at least one foaming surfactant.

The foaming surfactant contributes foaming properties to theantimicrobial composition, and may include anionic, cationic, nonionic,zwitterionic, or amphoteric surfactants and their associated salts. Anyfoaming surfactant may be employed, with the proviso that they will notdeleteriously affect the antimicrobial efficacy of the composition.Foaming surfactants suitable for alcoholic compositions are furtherdescribed in co-pending U.S. patent application Ser. No. 11/438,664,which is hereby incorporated by reference in its entirety.

In one embodiment, the foaming surfactant includes a fluorosurfactant, asiloxane polymer surfactant, or a combination thereof. Fluorosurfactantsinclude compounds that contain at least one fluorine atom. Examples offluorosurfactants include perfluoroalkylethyl phosphates,perfluoroalkylethyl betaines, fluoroaliphatic amine oxides,fluoroaliphatic sodium sulfosuccinates, fluoroaliphatic stearate esters,fluoroaliphatic phosphate esters, fluoroaliphatic quaternaries,fluoroaliphatic polyoxyethylenes, and the like, and mixtures thereof.

In one embodiment, the fluorosurfactant contains a charged species, i.e.is anionic, cationic, or zwitterionic. Examples of fluorosurfactantscontaining a charged species include perfluoroalkylethyl phosphates,perfluoroalkylethyl betaines, fluoroaliphatic amine oxides,fluoroaliphatic sodium sulfosuccinates, fluoroaliphatic phosphateesters, and fluoroaliphatic quaternaries. Specific examples offluorosurfactants include DEA-C8-18 perfluoroalkylethyl phosphate,TEA-C8-18 perfluoroalkylethyl phosphate, NH4-C8-18 perfluoroalkylethylphosphate, and C8-18 perfluoroalkylethyl betaine.

In one embodiment, the fluorosurfactant includes a compound that may berepresented by the formula

[F₃CF₂C—(CF₂CF₂)_(x)—CH₂CH₂—O—P₂O₃]⁻[R¹]⁺

where [R¹]⁺ includes DEA, TEA, NH₄, or betaine, and where x is aninteger from about 4 to about 18.

Siloxane polymer surfactants may be generally characterized bycontaining one or more Si—O—Si linkages in the polymer backbone. Thesiloxane polymer surfactant may or may not include a fluorine atom.Therefore, some foaming surfactants may be classified as bothfluorosurfactants and siloxane polymer surfactants. Siloxane polymersurfactants include organopolysiloxane dimethicone polyols, siliconecarbinol fluids, silicone polyethers, alkylmethyl siloxanes,amodimethicones, trisiloxane ethoxylates, dimethiconols, quaternizedsilicone surfactants, polysilicones, silicone crosspolymers, andsilicone waxes.

Examples of siloxane polymer surfactants include dimethicone PEG-7undecylenate, PEG-10 dimethicone, PEG-8 dimethicone, PEG-12 dimethicone,perfluorononylethyl carboxydecal PEG 10, PEG-20/PPG-23 dimethicone,PEG-11 methyl ether dimethicone, bis-PEG/PPG-20/20 dimethicone, siliconequats, PEG-9 dimethicone, PPG-12 dimethicone, fluoro PEG-8 dimethicone,PEG 23/PPG 6 dimethicone, PEG 20/PPG 23 dimethicone, PEG 17 dimethicone,PEG5/PPG3 methicone, bis PEG20 dimethicone, PEG/PPG20/15 dimethiconecopolyol and sulfosuccinate blends, PEG-8 dimethicone\dimmer acidblends, PEG-8 dimethicone\fatty acid blends, PEG-8 dimethicone\coldpressed vegetable oil\polyquaternium blends, random block polymers andmixtures thereof.

In one embodiment, the siloxane polymer surfactant includes a compoundthat may be represented by the formula

R₂—Si(CH₃)₂—[O—Si(CH₃)₂]_(a)—[O—Si (CH₃)R₃]_(b)—O—Si(CH₃)₂—R₂

where R₂ and R₃ independently include a methyl group or a moiety thatmay be represented by the formula

—(CH₂)₃—O—(CH₂CH₂O)_(c)—[CH₂CH(CH₃)O]_(d)—(CH₂CH₂O)_(e)H

with the proviso that both R₂ and R₃ are not CH₃, where a is an integerfrom about 3 to about 21, b is an integer from about 1 to about 7, c isan integer from about 0 to about 40, d is an integer from about 0 toabout 40, and e is an integer from about 0 to about 40, with the provisothat a>3×b and that c+d+e≧5.

The amount of foaming surfactant is not particularly limited, so long asan effective amount to produce foaming is present. In certainembodiments, the effective amount to produce foaming may vary, dependingupon the amount of alcohol and other ingredients that are present. Inone or more embodiments, the alcoholic composition includes at leastabout 0.002 wt. % of foaming surfactant, based upon the total weight ofthe antimicrobial composition. In another embodiment, the antimicrobialcomposition includes at least about 0.01 wt. % of foaming surfactant,based upon the total weight of the antimicrobial composition. In yetanother embodiment, the antimicrobial composition includes at leastabout 0.05 wt. % of foaming surfactant, based upon the total weight ofthe antimicrobial composition.

In one embodiment, the foaming surfactant is present in an amount offrom about 0.002 to about 4 weight percent, based upon the total weightof the antimicrobial composition. In another embodiment, the foamingsurfactant is present in an amount of from about 0.01 to about 2 weightpercent, based upon the total weight of the antimicrobial composition.It is envisioned that higher amounts may also be effective to producefoam. All such weights as they pertain to listed ingredients are basedon the active level, and therefore, do not include carriers orby-products that may be included in commercially available materials,unless otherwise specified.

In some embodiments, for economic or other reasons it may be desirableto limit the amount of fluorosurfactant used. Advantageously, stablefoam can be produced from a composition according to the presentinvention containing greater than about 60 wt. % alcohol, and from about0.002 to about 0.5 wt. % fluorosurfactant, based upon the total weightof the composition. In certain embodiments, the foamable compositionincludes greater than about 65 wt. % alcohol, and from about 0.002 toabout 0.4 wt. % fluorosurfactant, based upon the total weight of thecomposition.

In other embodiments, it may be desirable to use higher amounts offoaming surfactant. For example, in certain embodiments where thefoaming alcoholic composition of the present invention includes acleansing or sanitizing product that is applied to a surface and thenrinsed off, higher amounts of foaming surfactant may be employed. Inthese embodiments, the amount of foaming surfactant is present inamounts up to about 35 wt. %, based upon the total weight of thecomposition.

In one or more embodiments, the foaming surfactant is added directly tothe antimicrobial composition. In other embodiments, the foamingsurfactant is added to the antimicrobial composition as a solution oremulsion. In other words, the foaming surfactant may be premixed with acarrier to form a foaming surfactant solution or emulsion, with theproviso that the carrier does not deleteriously affect the foamingproperties of the antimicrobial composition. Examples of carriersinclude any of the carriers described hereinabove for the diolenhancers. It will be understood that, when the foaming surfactant ispremixed to form a foaming surfactant solution or emulsion, the amountof solution or emulsion that is added to the antimicrobial compositionmay be selected so that the amount of foaming surfactant falls withinthe ranges set forth hereinabove.

In certain embodiments, the alcoholic composition of the presentinvention further includes at least one foam booster. In one embodiment,the foam booster comprises a cationic oligomer or polymer, a collagenamino acid, an amaranth protein, or a soluble elastin. Foam boosters arefurther described in co-pending U.S. patent application Ser. No.12/032,083, which is hereby incorporated by reference in its entirety.

The foamable composition of the present invention may be employed in anytype of dispenser typically used for foam products. Advantageously,while the foamable composition can optionally be foamed by aerosolizingthe composition, an aerosolized product is not necessary for foaming.Any dispenser that is capable of mixing the foamable alcoholiccomposition with air or an inert gas may be used. Inert gases includegas that does not substantially react or otherwise deleteriously affectthe foamable composition. Examples of inert gases include nitrogen,argon, xenon, krypton, helium, neon, and radon. In one embodiment, thealcoholic composition is used in dispensers that employ foaming pumps,which combine ambient air or an inert gas and the alcoholic compositionin a mixing chamber and pass the mixture through a mesh screen.

In one or more embodiments, the viscosity of the composition is lessthan about 100 mPas, in one embodiment less than about 50 mPas, and inanother embodiment less than about 25 mPas.

In one or more embodiments, the antimicrobial composition may beformulated as a dispensable antimicrobial gel. In these embodiments, theantimicrobial composition may comprise a thickener, a neutralizer, and aplug-preventing additive, in addition to the alcohol and enhancer asdescribed hereinabove.

In one or more embodiments, the antimicrobial may be thickened withpolyacrylate thickeners such as those conventionally available and/orknown in the art. Examples of polyacrylate thickeners include carbomers,acrylates/C 10-30 alkyl acrylate crosspolymers, copolymers of acrylicacid and alkyl (C5-C10) acrylate, copolymers of acrylic acid and maleicanhydride, and mixtures thereof.

In one or more embodiments, the polymeric thickener includes from about0.5% to about 4% by weight of a cross-linking agent. Examples ofcross-linking agents include the polyalkenyl polyethers.

Commercially available polymers of the polyacrylate type include thosesold under the trade names Carbopol®, Acrysol® ICS-1, Polygel®,Sokalan®, Carbopol® 1623, Carbopol® 695, Ultrez 10, and Polygel® DB.

In one or more embodiments, the antimicrobial gel composition includesan effective amount of a polymeric thickener to adjust the viscosity ofthe antimicrobial gel to a viscosity range of from about 1000 to about65,000 centipoise. In one embodiment, the viscosity of the antimicrobialgel is from about 5000 to about 35,000, and in another embodiment, theviscosity is from about 10,000 to about 25,000. The viscosity ismeasured by a Brookfield RV Viscometer using RV and/or LV Spindles at 22oC+/−3 oC.

As will be appreciated by one of skill in the art, the effective amountof thickener will vary depending upon a number of factors, including theamount of alcohol and other ingredients in the antimicrobial gelcomposition. In one or more embodiments, an effective amount ofthickener is at least about 0.01 wt. %, based upon the total weight ofthe antimicrobial gel composition. In other embodiments, the effectiveamount is at least about 0.02 wt. %, in yet other embodiments at leastabout 0.05 wt. %, and it still other embodiments, at least about 0.1 wt.%.

In one embodiment, the effective amount of thickener is at least about0.5 wt. %, and in another embodiment, at least about 0.75 wt. %, basedupon the total weight of the antimicrobial gel. In one or moreembodiments, the compositions according to the present inventioncomprise up to about 10% by weight of the total composition of apolymeric thickener. In certain embodiments, the amount of thickener isfrom about 0.01 to about 1 wt. %, in another embodiment, from about 0.02to about 0.4 wt. %, and in another embodiment, from about 0.05 to about0.3 wt. %, based upon the total weight of the antimicrobial gel. In oneembodiment, the amount of thickener is from about 0.1 to about 10 wt. %,in another embodiment from about 0.5% to about 5% by weight, in anotherembodiment from about 0.75% to about 2% wt. %, based upon the totalweight of the antimicrobial gel.

In one or more embodiments, the antimicrobial gel may further comprise aneutralizer. The use of neutralizing agents to form salts of carbomerpolymers is known. Examples of neutralizing agents include amines,alkanolamines, alkanolamides, inorganic bases, amino acids, includingsalts, esters and acyl derivatives thereof.

Examples of common neutralizers are shown in Table 1, along with themanufacturers of these neutralizers, and the suggested ratio (per onepart polymeric thickener) to achieve neutralization (pH 7.0) when thepolymeric thickener has an equivalent weight of about 76+/−4.

TABLE 1 Neutralization Ratio Base/ Carbopol ® Trade Name CTFA NameManufacturer Polymer NaOH (18%) Sodium 2.3/1.0 Hydroxide AmmoniaAmmonium 0.7/1.0 (28%) Hydroxide KOH (18%) Potassium 2.7/1.0 HydroxideL-Arginine Arginine Ajinomoto 4.5/1.0 AMP-95 ® Aminomethyl Angus 0.9/1.0Propanol Neutrol ® TE Tetrahydro- BASF 2.3/1.0 xypropyl EthylenediamineTEA (99%) Triethanolamine 1.5/1.0 Tris Amino ® Tromethamine Angus3.3/1.0 (40%)* Ethomeen ® PEG-15 Akzo 6.2/1.0 C-25 CocamineDiisopropanol- Diisopropanol- Dow 1.2/1.0 amine amine Triisopropanol-Triisopropanol- Dow 1.5/1.0 amine amine

In one or more embodiments, the neutralizer may be selected based on theamount of alcohol that is to be gelled. Table 2 shows commonlyrecommended neutralizers for hydroalcoholic systems.

TABLE 2 Up to % Alcohol Neutralizer  20% Sodium Hydroxide  30% PotassiumHydroxide  60% Triethanolamine  60% Tris Amino  80% AMP-95 ®  90%Neutrol TE  90% Diisopropanolamine  90% Triisopropanolamine >90%Ethomeen C-25

In one or more embodiments, the antimicrobial composition furthercomprises one or more plug-preventing agents as co-additives. In one ormore embodiments, the antimicrobial composition comprises aplug-preventing co-additive that includes an ester having from 2 to 6ester groups or a polymeric ester that includes at least one estergroup. In one embodiment, the plug-preventing additive comprises amonomeric or polymeric di-ester, tri-ester, tetra-ester, penta-ester, orhexa-ester, or a polymeric monoester. Ester plug-preventing additivesare further described in co-pending International Patent Application No.PCT/US2008/081502, which is hereby incorporated by reference.

In one embodiment, the plug-preventing additive or co-additive ispresent in an amount of from about 0.005 to about 4 weight percentactive, based upon the total weight of the antimicrobial gelcomposition. In another embodiment, the plug-preventing additive ispresent in an amount of from about 0.01 to about 1 weight percent, basedupon the total weight of the antimicrobial gel composition, and in yetanother embodiment, the plug-preventing additive is present in an amountof from about 0.02 to about 0.7 weight percent, based upon the totalweight of the antimicrobial gel composition.

In one embodiment, the plug-preventing additive is added directly to theantimicrobial gel composition. In one or more other embodiments, theplug-preventing additive is added to the antimicrobial gel compositionas a solution or emulsion. In other words, the plug-preventing additivemay be premixed with a carrier to form a plug-preventing additivesolution or emulsion, with the proviso that the carrier does notdeleteriously affect the anti-clogging properties of the hydroalcoholicgel composition. Examples of carriers include water, alcohol, glycolssuch as propylene or ethylene glycol, ketones, linear and/or cyclichydrocarbons, triglycerides, carbonates, silicones, alkenes, esters suchas acetates, benzoates, fatty esters, glyceryl esters, ethers, amides,polyethylene glycols and PEG/PPG copolymers, inorganic salt solutionssuch as saline, and mixtures thereof. It will be understood that, whenthe plug-preventing additive is premixed to form a plug-preventingadditive solution or emulsion, the amount of solution or emulsion thatis added to the antimicrobial gel composition is selected so that theamount of plug-preventing additive falls within the ranges set forthhereinabove.

In one or more embodiments, the balance of the antimicrobial gelcomposition includes water or other suitable solvent. In one embodiment,one or more volatile silicone-based materials are included in theformulation to further aid the evaporation process. Exemplary volatilesilicones have a lower heat of evaporation than alcohol. In certainembodiments, use of silicone-based materials can lower the surfacetension of the fluid composition. This provides greater contact with thesurface. In one embodiment, the silicone-based material, such ascyclomethicone, trimethylsiloxy silicate or a combination thereof, maybe included in the formulation at a concentration of from about 4 wt. %to about 50 wt. % and in another embodiment from about 5 wt. % to about35 wt. %, and in yet another embodiment from about 11 wt. % to about 25wt. %, based upon the total weight of the antimicrobial gel composition.

The dispensable antimicrobial gel composition may be prepared by simplymixing the components together. The order of addition is notparticularly limited. In one embodiment, the antimicrobial gelcomposition is prepared by a method comprising dispersing the polymericthickener in alcohol with slow to moderate agitation, adding water, andthen adding a plug-preventing additive, and mixing until the mixture ishomogeneous. In other embodiments, the antimicrobial gel composition isprepared by a method comprising dispersing the polymeric thickener inwater with slow to moderate agitation, adding alcohol, a plug-preventingadditive, and mixing until the mixture is homogeneous. In one or moreembodiments, a neutralizer is added to the mixture to neutralize thethickener and form the gel. Those of skill in the art will understandthat optional ingredients may be added at various points during themixing process. It will also be understood that a gel may be formedwithout a neutralizer if the thickener is one that swells when mixedwith water or alcohol.

The antimicrobial gel composition of the present invention may beemployed in any type of dispenser typically used for gel products, forexample pump dispensers. A wide variety of pump dispensers are suitable.Pump dispensers may be affixed to bottles or other free-standingcontainers. Pump dispensers may be incorporated into wall-mounteddispensers. Pump dispensers may be activated manually by hand or footpump, or may be automatically activated. Useful dispensers include thoseavailable from GOJO Industries under the designations NXT® and TFX™ aswell as traditional bag-in-box dispensers. Examples of dispensers aredescribed in U.S. Pat. Nos. 5,265,772, 5,944,227, 6,877,642, 7,028,861,and U.S. Published Application Nos. 2006/0243740 A1 and 2006/0124662 A1,all of which are incorporated herein by reference. In one or moreembodiments, the dispenser includes an outlet such as a nozzle, throughwhich the antimicrobial gel composition is dispensed.

In one or more embodiments, the antimicrobial composition is a wipecomposition. Wipe antimicrobial alcoholic compositions in accordancewith this invention include at least one alcohol, a C₁₋₁₀ alkane diolenhancer, and are applied to a wipe substrate.

Wipe substrates used in antimicrobial wipes are further described inU.S. Pat. Nos. 5,686,088, 6,410,499, 6,436,892, 6,495,508, 6,844,308. Inone or more embodiments, the wipe may comprise a laminate formed byspunbonding/meltblowing/spunbonding (SMS). Generally, an SMS materialcontains a meltblown web sandwiched between two exteriors spunbond webs.SMS materials are further described in U.S. Pat. Nos. 4,041,203,5,169,706, 5,464,688, and 4,766,029, and are commercially available, forexample from Kimberly-Clark Corporation under marks such as Spunguard 7and Evolution 7. The SMS laminate may be treated or untreated.

As described hereinabove, the antimicrobial composition of thisinvention includes an alcohol and an enhancer. The composition canfurther comprise a wide range of optional ingredients, with the provisothat they do not deleteriously affect the sanitizing efficacy of thecomposition. By deleterious is meant that the decrease in the logreduction according to the FDA TFM healthcare personnel hand wash testis not de minimus, or in other words, the log reduction does notdecrease by more than about 0.5. The CTFA International CosmeticIngredient Dictionary and Handbook, Eleventh Edition 2005, and the 2004CTFA International Buyer's Guide, both of which are incorporated byreference herein in their entirety, describe a wide variety ofnon-limiting cosmetic and pharmaceutical ingredients commonly used inthe skin care industry, that are suitable for use in the compositions ofthe present invention. Nonlimiting examples of functional classes ofingredients are described at page 537 of this reference. Examples ofthese functional classes include: abrasives, anti-acne agents,anticaking agents, antioxidants, binders, biological additives, bulkingagents, chelating agents, chemical additives; colorants, cosmeticastringents, cosmetic biocides, denaturants, drug astringents,emulsifiers, external analgesics, film formers, fragrance components,humectants, opacifying agents, plasticizers, preservatives (sometimesreferred to as antimicrobials), propellants, reducing agents, skinbleaching agents, skin-conditioning agents (emollient, miscellaneous,and occlusive), skin protectants, solvents, surfactants, foam boosters,hydrotropes, solubilizing agents, suspending agents (nonsurfactant),sunscreen agents, ultraviolet light absorbers, detackifiers, andviscosity increasing agents (aqueous and nonaqueous). Examples of otherfunctional classes of materials useful herein that are well known to oneof ordinary skill in the art include solubilizing agents, sequestrants,keratolytics, topical active ingredients, and the like.

In certain embodiments, the antimicrobial composition comprises one ormore humectants. Examples of humectants include propylene glycol,dipropyleneglycol, hexylene glycol, 1,4-dihydroxyhexane,1,2,6-hexanetriol, sorbitol, butylene glycol, propanediols, such asmethyl propane diol, dipropylene glycol, triethylene glycol, glycerin(glycerol), polyethylene glycols, ethoxydiglycol, polyethylene sorbitol,and combinations thereof. Other humectants include glycolic acid,glycolate salts, lactate salts, lactic acid, sodium pyrrolidonecarboxylic acid, hyaluronic acid, chitin, and the like. In oneembodiment, the humectant is present in an amount of from about 0.1 toabout 20% by weight, based upon the total weight of the antimicrobialcomposition. In another embodiment the humectant is present in an amountof from about 1 to about 8% by weight, in another embodiment from about2 to about 3% by weight, based upon the total weight of theantimicrobial composition.

In these or other embodiments, the antimicrobial composition comprisesone or more conditioning or moisturizing esters. Examples of estersinclude cetyl myristate, cetyl myristoleate, and other cetyl esters,diisopropyl sebacate, and isopropyl myristate. In one embodiment, theester is present in an amount of up to 10% by weight, based upon thetotal weight of the antimicrobial composition. In another embodiment theester is present in an amount of from about 0.5 to about 5% by weight,in another embodiment from about 1 to about 2% by weight, based upon thetotal weight of the antimicrobial composition.

In one or more embodiments, the antimicrobial composition includes oneor more emulsifying agents. Examples of emulsifying agents includestearyl alcohol, sorbitan oleate trideceth-2, poloxamers, andPEG/PPG-20/6 dimethicone. In one embodiment, the emulsifying agent ispresent in an amount of up to about 10% by weight, based upon the totalweight of the antimicrobial composition. In another embodiment theemulsifying agent is present in an amount of from about 0.1 to about 5%by weight, in another embodiment from about 0.5 to about 2% by weight,based upon the total weight of the antimicrobial composition.

In one embodiment, the antimicrobial composition includes one or morethickeners and optionally one or more stabilizers. Examples ofthickeners and stabilizers include hydroxyethyl cellulose hydroxypropylcellulose, methyl cellulose, carboxymethyl cellulose, and ammoniumacryloyldimethyltaurate/VP copolymer. In one embodiment, where thethickener or stabilizer is starch-based, the thickener or stabilizer ispresent in an amount of up to about 10% by weight, in another embodimentin an amount of from about 0.1 to about 5% by weight, in yet anotherembodiment from about 0.2 to about 1% by weight, based upon the totalweight of the antimicrobial composition. In other embodiments, where thethickener or stabilizer is a synthetic polymer, the thickener orstabilizer is present in an amount of up to about 15% by weight, inanother embodiment in an amount of from about 0.1 to about 10% byweight, in yet another embodiment from about 1 to about 2% by weight,based upon the total weight of the antimicrobial composition.

In one or more embodiments, the antimicrobial composition includes oneor more solubilizers. Examples of solubilizers include PEG-40hydrogenated castor oil, polysorbate-80, PEG-80 sorbitan laurate,ceteareth-20, oleth-20, PEG-4, and propylene glycol. The amount ofsolubilizer is not particularly limited, so long as it does notdeleteriously affect the sanitizing efficacy of the composition.

In one or more embodiments, the antimicrobial composition includes oneor more antiviral agents or antiviral enhancers. Examples of antiviralagents include botanicals such as rosmarinic acid,tetrahydrocurcuminoids, oleuropen, oleanolic acid, aspalathus linearisextract, white tea, red tea, green tea extract, neem oil limonoids,coleus oil, licorice extract, burnt, ginger & cinnamon extracts,alpha-glucan oligosaccharide, perilla ocymoides leaf powder, camphor,camellia oleifera leaf extract, ginger, menthol, eucalyptus, capillisilhc, hydroxyprolisilane cn, sandlewood oil/resin, calendula oil, rosemaryoil, lime/orange oils, and hop acids. When used, the antiviral agentsare present in amounts of from about 0.1 to about 1 percent by weight,based upon the total weight of the antimicrobial composition.

Examples of antiviral enhancers include proton donors, cationicoligomers and polymers, chaotropic agents, and copper and zinccompounds. Antiviral enhancers are further described in co-pending U.S.Patent Application Publications 2007/0184013, 2007/0185216, and2009/0018213, all of which are hereby incorporated by reference.

It has been discovered that the combination of alcohol and enhancerexhibits enhanced antimicrobial efficacy. Advantageously, auxiliaryantimicrobials, some of which can be harsh on skin, are not required. Incertain embodiments, the antimicrobial composition does not contain anyauxiliary antimicrobial ingredients. Any antimicrobial ingredient otherthan the combination of alcohol and enhancer may be referred to as anauxiliary antimicrobial agent. In one embodiment, the amount ofauxiliary antimicrobial agent (including preservatives) is less thanabout 0.1 wt. %, in another embodiment, less than about 0.05 wt. %,based upon the total weight of the antimicrobial composition. In anotherembodiment, the antimicrobial composition is devoid of auxiliaryantimicrobial agents.

It is envisioned that, in other embodiments, auxiliary antimicrobialagents could be included, with the proviso that the antimicrobialingredient does not deleteriously affect the sanitizing properties ofthe composition. Examples of auxiliary antimicrobial agents include, butare not limited to, triclosan, also known as5-chloro-2(2,4-dichlorophenoxy) phenol (PCMX) and available fromCiba-Geigy Corporation under the tradename IRGASAN®; chloroxylenol, alsoknown as 4-chloro-3,5-xylenol, available from Nipa Laboratories, Inc.under the tradenames NIPACIDE® MX or PX; hexetidine, also known as5-amino-1,3-bis(2-ethylhexyl)-5-methyl-hexahydropyrimidine;chlorhexidine salts including chlorhexidine gluconate and the salts ofN,N″-Bis (4 -chlorophenyl)-3,12 -diimino-2,4,11,14-tetraazatetradecanediimidi amide; 2-bromo-2-nitropropane-1;3-diol, benzalkonium chloride; cetylpyridinium chloride;alkylbenzyldimethylammonium chlorides; iodine; phenol, bisphenol,diphenyl ether, phenol derivatives, povidone-iodine includingpolyvinylpyrrolidinone-iodine; parabens; hydantoins and derivativesthereof, including 2,4-imidazolidinedione and derivatives of2,4-imidazolidinedione as well as dimethylol-5,5-dimethylhydantoin (alsoknown as DMDM hydantoin or glydant); phenoxyethanol; cis isomer of1-(3-chloroallyl)-3,5,6-triaza-l-azoniaadamantane chloride, also knownas quatemium-15 and available from Dow Chemical Company under thetradename DOWCIL™ 2000; diazolidinyl urea; benzethonium chloride;methylbenzethonium chloride; glyceryl laurate, transition metalcompounds such as silver, copper, magnesium, zinc compounds, hydrogenperoxide, chlorine dioxide, anilides, bisguanidines, tropolone, andmixtures thereof. When used, the auxiliary antimicrobial agents arepresent in amounts of from about 0.1 to about 1 wt. %, based upon thetotal weight of the antimicrobial composition.

Advantageously, certain ingredients that have been designated ascritical to current antiseptic compositions can be limited in theantimicrobial composition of the present invention. For example, zinccompounds such as organic salts of zinc, zinc gluconate, zincpyrithione, or zinc omadine are not necessary, and can be limited, ifdesired, to less than about 0.5 wt. %, or in another embodiment to lessthan about 0.1 wt. %, based upon the total weight of the antimicrobialcomposition. In another embodiment, the antimicrobial composition isdevoid of organic salts of zinc.

In one or more embodiments, the amount of acid may be limited. Morespecifically, in one or more embodiments, the amount of organic acid maybe limited. In one or more embodiments, the amount of any of thefollowing acids may be limited: citric acid, glycolic acid, lactic acid,malic acid, tartaric acid, and acetic acid. When limited, in one or moreembodiments, the amount of acid may be less than 0.125 wt. %, in otherembodiments less than about 0.08 wt. %, based upon the total weight ofthe antimicrobial composition. In another embodiment, the antimicrobialcomposition is devoid of citric acid, glycolic acid, lactic acid, malicacid, tartaric acid, and acetic acid.

In one or more embodiments, the amount of essential oil is less than 0.1wt. %, or in another embodiment less than about 0.05 wt. %, based uponthe total weight of the antimicrobial composition. In anotherembodiment, the antimicrobial composition is devoid of essential oils.More specifically, in one embodiment, the antimicrobial compositioncontains less than 0.1 wt. %, in another embodiment less than 0.05, andin another embodiment, is devoid of any of the following essential oils:cinnamon oil, basil oil, bergamot oil, clary sage oil, ylang-ylang oil,neroli oil, sandalwood oil, frankincense oil, ginger oil, peppermintoil, lavender oil, jasmine absolute, geranium oil bourbon, spearmintoil, clove oil, patchouli oil, rosemary oil, rosewood oil, sandalwoodoil, tea tree oil, vanilla oil, lemongrass oil, cedarwood oil, balsamoils, tangerine oil, Hinoki oil, Hiba oil, ginko oil, eucalyptus oil,lemon oil, orange oil, sweet orange oil, and calendula oil, wherein theabove amounts are based upon the total weight of the antimicrobialcomposition.

In one or more embodiments, the amount of specific constituents ofessential oils is also limited. More specifically, in one embodiment,the antimicrobial composition contains less than 0.1 wt. %, in anotherembodiment less than 0.05, and in another embodiment, is devoid of anyof the following constituents of essential oils: farnesol, nerolidol,bisabolol, apritone, chamazulene, santalol, zingiberol, carotol, andcaryophyllen, curcumin, 1-citronellol, α-amylcinnarnaldehyde, lyral,geraniol, farnesol, hydroxycitronellal, isoeugenol, eugenol, camphor,eucalyptol, linalool, citral, thymol, limonene and menthol, wherein theabove amounts are based upon the total weight of the antimicrobialcomposition.

Advantageously, traditional preservative agents are not required. In oneor more embodiments, the amount of traditional preservative agents suchas potassium sorbate, parabens, and iodopropynyl butylcarbomate (IPBC)is limited. In one or more embodiments, the antimicrobial compositioncontains less than about 0.1 wt. %, in another embodiment less thanabout 0.05 wt. %, or in another embodiment less than about 0.01 wt. % oftraditional preservative agents, based upon the total weight of theantimicrobial composition. In another embodiment, the antimicrobialcomposition is devoid of traditional preservative agents.

Indeed, any component other than the alcohol and diol enhancer is notnecessary to achieve antimicrobial efficacy and can optionally belimited to less than about 0.5 wt. %, if desired to less than about 0.1wt. %, if desired to less than about 0.01 wt. %, or if desired to lessthan about 0.001 wt. %. It will be understood that the balance of theantimicrobial composition may, in certain embodiments, include water orother suitable solvent. In one embodiment, the antimicrobial compositionis devoid of any component other than alcohol, diol enhancer andoptionally water or other suitable solvent.

The antimicrobial composition may be prepared by simply mixing thecomponents together. In one embodiment, where one or more components isobtained as a solid powder, the antimicrobial composition is prepared bya method comprising dispersing the solid powder in water to form a gel,adding alcohol with slow to moderate agitation, and then adding otheringredients as desired, and mixing until the mixture is homogeneous.

As stated hereinabove, the antimicrobial composition of the presentinvention may be embodied in a variety of forms, including as a liquid,gel, foam or wipe composition. Surprisingly, it has been found that theviscosity of the liquid antimicrobial composition does not affect thesanitizing efficacy of the composition. For example, in one or moreembodiments of the present invention, the same amount of log reductionis achieved with a liquid antimicrobial composition having a viscosityof 5 centipoise (cPs) and an antimicrobial composition having aviscosity of about 2000 cPs. Thus it will be understood that theviscosity of the antimicrobial composition of the present invention isnot limited.

In one embodiment, where the antimicrobial composition is in liquidform, the percent solids of the antimicrobial composition is less thanabout 6 percent, in another embodiment, less than about 5 percent, inyet another embodiment, less than about 4 percent, in still anotherembodiment, less than about 3 percent, in another embodiment, less thanabout 2 percent, in yet another embodiment, less than about 1 percent.The percent solids can be determined by various methods known in theart.

In one or more embodiments, the pH of the antimicrobial composition isfrom about 1.5 to about 10, in another embodiment from about 4.5 toabout 9.5, in another embodiment from about 7 to about 8.

Unexpectedly, when an enhancer is combined with alcohol according to thepresent invention, rapid antimicrobial activity is enhanced, i.e.potentiated. In one or more embodiments, the antimicrobial compositionis effective in killing gram negative and gram positive bacteria, fungi,parasites, non-enveloped and enveloped viruses. In one or moreembodiments, the antimicrobial composition has rapid antimicrobialefficacy against bacteria such as Staphylococcus aureus,methicillin-resistant S. aureus, Escherichia coli, Pseudomonasaeruginosa, Serratia marcescens, and fungi such as Candida albicans andAspergillus niger. In one or more embodiments, the antimicrobialcomposition has rapid efficacy against skin microflora, includingresident and transient skin microflora.

Thus, the present invention further provides a method for killing orinactivating microbes on a surface comprising applying, to the surface,an effective amount of an antimicrobial composition as described herein.The antimicrobial composition may be employed on a wide variety ofsurfaces or substrates, including skin, porous, and non-porous surfaces.

In one or more embodiments, the antimicrobial composition of the presentinvention is applied topically to mammalian skin. In these embodiments,the composition is not applied to the eyes, ears, nose, mouth, or anymembranes thereof. In one embodiment, the methods of bringing theantimicrobial composition into contact with a microbe on human skinincludes applying an amount of the composition to the skin, and allowingthe composition to remain in contact with the skin for a suitable amountof time. In other embodiments, the composition may be spread over thesurface of the skin, rubbed in, rinsed off, allowed to dry viaevaporation, or wiped off

Thus, the present invention provides a method for skin sanitization, themethod comprising contacting mammalian skin with an effective amount ofan antimicrobial composition comprising at least 30 wt. % alcohol, basedupon the total weight of the antimicrobial composition, and anefficacy-enhancing amount of at least one C₆₋₁₀ alkane diol. In one ormore embodiments, the present invention provides a method for handsanitization.

Advantageously, the antimicrobial composition of the present inventionmay be used as a healthcare personnel hand wash. In one or moreembodiments, the present invention provides an antimicrobial compositionthat meets the standards of the FDA Tentative Final Monograph forHealthcare Antiseptic Drug Products (TFM) (Federal Register 59 [116],Jun. 17, 1994: pp. 31402-31452) for healthcare personnel hand wash.

In the FDA TFM test for healthcare personnel hand wash and otherstandard tests, test procedures include multiple wash cycles. In eachcycle, a subject surface is contaminated with a test organism and thesurface is washed with a test product. After a specified number of washcycles, the surface is rinsed and the rinsing liquid is tested todetermine what log reduction has been achieved by the test product. Forexample, in the FDA TFM test for healthcare personnel hand wash, thefollowing protocol is followed for leave on products such as alcoholiccompositions. The hands of a test subject are contaminated with a testorganism such as Serratia marcescens, and washed using the test product.The hands are then placed into sterile gloves, a bacterial recoverysolution is added and hands are massaged by a technician for a presetamount of time to recover viable bacteria from the hands. The recoverysolution is plated to determine the log reduction achieved by one wash.The hands of the test subject are again contaminated with the testorganism and washed using the test product. For a third time the handsof the test subject are again contaminated with the test organism andwashed using the test product. After the third wash the hands are againplaced into gloves and viable bacteria are recovered to determine thelog reduction after the third wash. The cycle of contamination and washis repeated until, after the seventh wash, the hands are again placedinto gloves and viable bacteria are recovered to determine the logreduction after the seventh wash. The cycle of contamination and wash isrepeated until, after the tenth wash, the hands are again placed intogloves and viable bacteria are recovered to determine the log reductionafter the tenth wash. According to the FDA TFM test, healthcarepersonnel hand wash formulations must reduce the number of bacteria onthe hands by 2 log₁₀ after one wash and reduce the number of bacteria onthe hands by 3 log₁₀ after ten washes. It should be noted that the FDATFM test refers to “wash” for both rinse-off and leave-on products, andtherefore the instant specification may do the same.

Many alcoholic products achieve a minimum 3 log reduction after one washusing the FDA TFM test. However, many alcoholic products fail to achievea minimum of 3 log reduction after the tenth wash using the FDA TFMtest. In fact, a number of alcoholic products exhibit a reduction in logreduction over successive washes.

Advantageously, the enhanced alcoholic compositions of the presentinvention do not exhibit a reduction in efficacy over successive washes,when tested according to the FDA TFM healthcare personnel hand wash orsimilar protocol.

In one or more embodiments, the antimicrobial composition of the presentinvention meets or exceeds the requirement of 2 log₁₀ reduction after afirst wash, and 3 log₁₀ reduction after a tenth wash. In one or moreembodiments, enhanced alcoholic compositions according to the presentinvention provide a log reduction of at least about 3 after one wash,and at least about 3 after ten washes. In certain embodiments, theantimicrobial composition demonstrates a cumulative effect and surpassesthe requirements of the FDA TFM healthcare personnel hand wash test byachieving 3 log₁₀ reduction after wash 1 and 4 log₁₀ reduction afterwash 10.

In one or more embodiments, the log₁₀ reduction of a test organismachieved by a third wash utilizing the enhanced composition of thepresent invention is at least equal to the log₁₀ reduction achieved by afirst wash cycle. In one or more embodiments, the log₁₀ reduction of atest organism achieved by a tenth wash utilizing the enhancedcomposition of the present invention is at least equal to the log₁₀reduction achieved by a first wash cycle.

When evaluated according to tests that require multiple wash cycleprotocols, enhanced alcoholic compositions according to the presentinvention provide a log reduction that is maintained or even improvedover multiple wash cycles. Furthermore, the enhanced compositionunexpectedly provides cumulative activity, i.e. the efficacy of theenhanced composition increases with multiple uses.

The sustained efficacy exhibited by the enhanced alcoholic antimicrobialcompositions of the present invention make them useful as surgical scrubcompositions. Requirements for in vitro and in vivo testing of surgicalhand scrubs are outlined in the FDA Tentative Final Monograph forHealthcare Antiseptic Drug Products (TFM) (Federal Register 59 [116],Jun. 17, 1994: pp. 31445-31448). The in vivo test procedure describedbeginning on page 31445 will hereinafter be referred to as the FDA TFMsurgical hand scrub test. The antimicrobial efficacy of Surgical Scrubscan also be tested by any appropriate recognized test to demonstrateadequate disinfection of resident skin flora. Examples of such tests areASTM E 1115-02, “Standard Test Method for Evaluation of Surgical HandScrub Formulations” (ASTM International) and EN 12791:2005, “Chemicaldisinfectants and antiseptics, Surgical hand disinfection, Test methodand requirement (phase 2, step 2),” (CEN-Comitee Europeen deNormalisation, Brussels, Belgium).

The antimicrobial composition and method of the present inventionprovides rapid antimicrobial efficacy upon a single use, withoutrequiring auxiliary antimicrobial agents. The rapid, broad-spectrumefficacy makes the compositions useful as skin preparations as describedand tested in ASTM E 1173-01 provides “Standard Test Method forEvaluation of Preoperative, Precatheterization, or Preinjection SkinPreparations” and FDA Tentative Final Monograph for HealthcareAntiseptic Drug Products (TFM) (Federal Register 59 [116], Jun. 17,1994: pp. 31402-31452).

In one or more embodiments, the present invention provides anantimicrobial composition that meets the standards of one or more ofEN1040 for basic bactericidal activity, EN1275 for basic fungicidalactivity, EN1500 for activity of products for use as a hygienic handrub, EN 14348 for tuberculoidal activity, EN 14476 for virucidalactivity, and EN12791 for surgical hand disinfection.

More generally, in one or more embodiments, the method provides a logreduction of transient skin microflora of at least about 1 in less thanabout 1 minute. In other embodiments, the method provides a logreduction of transient skin microflora of at least about 2 in less thanabout 1 minute. In yet other embodiments, the method provides a logreduction of transient skin microflora of at least about 3 in less thanabout 1 minute. In other embodiments, the method provides a logreduction of transient skin microflora of at least about 4 in less thanabout 1 minute. In yet other embodiments, the method provides a logreduction of transient skin microflora of at least about 5 in less thanabout 1 minute.

In one or more embodiments, the method provides a log reduction againsttransient skin microflora of at least about 1 in less than about 30seconds. In other embodiments, the method provides a log reductionagainst transient skin microflora of at least about 2 in less than about30 seconds. In yet other embodiments, the method provides a logreduction against transient skin microflora of at least about 3 in lessthan about 30 seconds. In other embodiments, the method provides a logreduction against transient skin microflora of at least about 4 in lessthan about 30 seconds. In yet other embodiments, the method provides alog reduction against transient skin microflora of at least about 5 inless than about 30 seconds.

In one or more embodiments, the method provides a log reduction againsttransient skin microflora of at least about 1 in less than about 15seconds. In other embodiments, the method provides a log reductionagainst transient skin microflora of at least about 2 in less than about15 seconds. In yet other embodiments, the method provides a logreduction against transient skin microflora of at least about 3 in lessthan about 15 seconds. In other embodiments, the method provides a logreduction against transient skin microflora of at least about 4 in lessthan about 15 seconds. In yet other embodiments, the method provides alog reduction against transient skin microflora of at least about 5 inless than about 15 seconds.

In one or more embodiments, the method provides a log reduction againstEscherichia coli of at least about 1 in less than about 1 minute. Inother embodiments, the method provides a log reduction againstEscherichia coli of at least about 2 in less than about 1 minute. In yetother embodiments, the method provides a log reduction against themixture of at least about 3 in less than about 1 minute. In otherembodiments, the method provides a log reduction against Escherichiacoli of at least about 4 in less than about 1 minute. In yet otherembodiments, the method provides a log reduction against Escherichiacoli of at least about 5 in less than about 1 minute.

In one or more embodiments, the method provides a log reduction againstEscherichia coli of at least about 1 in less than about 30 seconds. Inother embodiments, the method provides a log reduction againstEscherichia coli of at least about 2 in less than about 30 seconds. Inyet other embodiments, the method provides a log reduction againstEscherichia coli of at least about 3 in less than about 30 seconds. Inother embodiments, the method provides a log reduction againstEscherichia coli of at least about 4 in less than about 30 seconds. Inyet other embodiments, the method provides a log reduction againstEscherichia coli of at least about 5 in less than about 30 seconds.

In one or more embodiments, the method provides a log reduction againstEscherichia coli of at least about 1 in less than about 15 seconds. Inother embodiments, the method provides a log reduction againstEscherichia coli of at least about 2 in less than about 15 seconds. Inyet other embodiments, the method provides a log reduction againstEscherichia coli of at least about 3 in less than about 15 seconds. Inother embodiments, the method provides a log reduction againstEscherichia coli of at least about 4 in less than about 15 seconds. Inyet other embodiments, the method provides a log reduction againstEscherichia coli of at least about 5 in less than about 15 seconds.

In one or more embodiments, the method provides a log reduction againstSerratia marcescens of at least about 1 in less than about 1 minute. Inother embodiments, the method provides a log reduction against Serratiamarcescens of at least about 2 in less than about 1 minute. In yet otherembodiments, the method provides a log reduction against the mixture ofat least about 3 in less than about 1 minute. In other embodiments, themethod provides a log reduction against Serratia marcescens of at leastabout 4 in less than about 1 minute. In yet other embodiments, themethod provides a log reduction against Serratia marcescens of at leastabout 5 in less than about 1 minute.

In one or more embodiments, the method provides a log reduction againstSerratia marcescens of at least about 1 in less than about 30 seconds.In other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 2 in less than about 30 seconds.In yet other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 3 in less than about 30 seconds.In other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 4 in less than about 30 seconds.In yet other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 5 in less than about 30 seconds.

In one or more embodiments, the method provides a log reduction againstSerratia marcescens of at least about 1 in less than about 15 seconds.In other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 2 in less than about 15 seconds.In yet other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 3 in less than about 15 seconds.In other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 4 in less than about 15 seconds.In yet other embodiments, the method provides a log reduction againstSerratia marcescens of at least about 5 in less than about 15 seconds.

More generally, in one or more embodiments, the method provides a logreduction of resident skin microflora of at least about 1 in less thanabout 1 minute. In other embodiments, the method provides a logreduction of resident skin microflora of at least about 2 in less thanabout 1 minute. In yet other embodiments, the method provides a logreduction of resident skin microflora of at least about 3 in less thanabout 1 minute. In other embodiments, the method provides a logreduction of resident skin microflora of at least about 4 in less thanabout 1 minute. In yet other embodiments, the method provides a logreduction of resident skin microflora of at least about 5 in less thanabout 1 minute.

In one or more embodiments, the method provides a log reduction againstresident skin microflora of at least about 1 in less than about 30seconds. In other embodiments, the method provides a log reductionagainst resident skin microflora of at least about 2 in less than about30 seconds. In yet other embodiments, the method provides a logreduction against resident skin microflora of at least about 3 in lessthan about 30 seconds. In other embodiments, the method provides a logreduction against resident skin microflora of at least about 4 in lessthan about 30 seconds. In yet other embodiments, the method provides alog reduction against resident skin microflora of at least about 5 inless than about 30 seconds.

In one or more embodiments, the method provides a log reduction againstresident skin microflora of at least about 1 in less than about 15seconds. In other embodiments, the method provides a log reductionagainst resident skin microflora of at least about 2 in less than about15 seconds. In yet other embodiments, the method provides a logreduction against resident skin microflora of at least about 3 in lessthan about 15 seconds. In other embodiments, the method provides a logreduction against resident skin microflora of at least about 4 in lessthan about 15 seconds. In yet other embodiments, the method provides alog reduction against resident skin microflora of at least about 5 inless than about 15 seconds.

Any amount of the antimicrobial composition may be used for eachapplication, so long as it is at least an effective amount to contactsubstantially the entire target surface and keep it wet for at least 15to 30 seconds. In one embodiment, an effective amount is at least about1.5 milliliters (mL), in another embodiment at least about 2 mL, in yetanother embodiment, at least about 2.5 mL, in yet another embodiment, atleast about 3.0 mL, in yet another embodiment, at least about 4.5 mL,and in yet another embodiment, at least about 5 mL. Advantageously, theeffective amount of antimicrobial composition according to the presentinvention, i.e. the minimum amount necessary to contact substantiallythe entire target surface, is also an amount that is effective toachieve adequate efficacy. Other products may not achieve adequateefficacy if only an effective amount to contact substantially the entiretarget surface is used. It will be understood that it is advantageous toachieve adequate efficacy while using a small amount of product. This istrue for economic reasons, as well as because the amount of timerequired for the product to be rubbed into the skin and orevaporated/dried is reduced when less product is used.

Advantageously, in one or more embodiments, the present inventionfurther provides compositions and methods with rapid antimicrobialefficacy against gram positive and gram negative bacteria and fungi, aswell as broad spectrum virucidal efficacy against one or more envelopedor one or more non-enveloped viruses. Examples of enveloped virusesinclude Herpes virus, Influenza virus; Paramyxovirus, Respiratorysyncytial virus, Corona virus, HIV, Hepatitis B virus, Hepatitis Cvirus, SARS-CoV, and Toga virus. Non-enveloped viruses, sometimesreferred to as “naked” viruses, include the families Picornaviridae,Reoviridae, Caliciviridae, Adenoviridae and Parvoviridae. Members ofthese families include Rhinovirus, Poliovirus, Adenovirus, Hepatitis Avirus, Norovirus, Papillomavirus, and Rotavirus.

In one or more embodiments, the method comprises contacting enveloped ornon-enveloped virus particles with an enhanced alcoholic compositioncomprising a C₁₋₆ alcohol, a C₆₋₁₀ alkane diol, and anefficacy-enhancing amount of one or more antiviral enhancers selectedfrom the group consisting of cationic oligomers and polymers, protondonors, chaotropic agents, and mixtures thereof. Antiviral enhancers arefurther described in co-pending published patent application nos. U.S.2007/0185216 and 2007/0184013, both of which are hereby incorporated byreference.

In order to demonstrate the practice of the present invention, thefollowing examples have been prepared and tested. The examples shouldnot, however, be viewed as limiting the scope of the invention. Theclaims will serve to define the invention.

EXAMPLES

Examples 1-3 were foamable formulations that were dispensed as foams.Example 1 contained 70 wt. % ethanol, and conventional amounts of PEG-10dimethicone, PEG-12 dimethicone, glycerin, fragrance, propylene glycol,isopropyl myristate, and tocopheryl acetate. The composition of Example2 was identical to Example 1 except that Example 2 also included 0.5 wt.% 1,2-octanediol. Example 3 contained 62 wt. % ethanol, 0.5 wt. %1,2-octanediol, and conventional amounts of PEG-10 dimethicone, PEG-12dimethicone, glycerin, fragrance, propylene glycol, isopropyl myristate,and tocopheryl acetate. Example 4 was a commercially available liquidformulation that contained about 63% by volume isopropanol, and ismarketed by Steris Corporation under the trademark CalStatC. Inactiveingredients include deionized water, methylpropanediol, phenoxyethanol,cetyl lactate, glycerin, hydroxypropyl cellulose polyquaternium-6,behentrimonium methosulfate, and fragrascent powder.

The Examples were tested under the FDA TFM healthcare personnel handwash hand scrub test. Here, 8 participants were used for testing. Anappropriate volume of the sample to be tested was placed into the palmof one hand and spread evenly over all aspects of the hand and wrist,paying particular attention to the space under the nails, cuticles, andinterdigital spaces. The participants were instructed to rub their handsvigorously until dry. The critical performance properties for the testproducts are: a 2 log₁₀ reduction in the concentration of the markerorganism (Serratia marcescens) following first wash, and a 3 log₁₀reduction in the concentration of the marker organism (Serratiamarcescens) following 10th wash.

The antimicrobial efficacy test data for Examples 1-4 is presented inTable 3. It can be seen that, for Example 1, the efficacy declines withmultiple wash cycles, whereas for Example 2, the efficacy increases.

TABLE 3 MEAN log10 REDUCTION MEAN log10 REDUCTION EXAMPLE WASH 1 WASH 101 4.26 3.56 2 4.29 4.75 3 4.46 4.92 4 4.44 4.97

Examples 5-7 were hydroalcoholic gel formulations. Example 5 contained70 wt. % ethanol, and conventional amounts of acrylates, crosspolymer,aminomethyl propanol, and white unispheres. The composition of Example 6was identical to Example 5, except that Example 6 included 0.5 wt. %1,2-octanediol. The composition of Example 7 was identical to Example 5,except that Example 7 included 1 wt. % decylene glycol.

Examples 5-7 were tested as above for Examples 1-4.

TABLE 4 log₁₀ REDUCTION log₁₀ REDUCTION EXAMPLE WASH 1 WASH 10 5 3.693.29 6 3.97 4.30 7 4.30 4.11

Examples 8-14 contained 35 wt. % ethanol in water. Examples 9-14additionally contained 2 wt. % of a 1,2-alkane diol, as summarized inthe Table below. In vitro efficacy of these compositions was measuredagainst a mixture of E. coli, S. aureus, E. faecium, and S. marcescens(Group 1). Efficacy was also measured against a mixture of S. aureus(MRSA), P. mirabilis, K. pneumoniae, and S. epidermidis (Group 2). Thetest was conducted according to the ASTM E 2315 method, “Standard Guidefor Assessment of Antimicrobial Activity Using a Time-Kill Procedure.”Contact time was 15 seconds. Results are summarized in the table below.It can be seen that alkane diols above a 5 chain carbon lengthpotentiate the rapid antimicrobial activity of alcohol whereas alkanediols below 5 chain carbon length do not.

TABLE 5 EXAM- log₁₀ REDUCTION log₁₀ REDUCTION PLE 1,2-alkane diol GROUP1 GROUP 2 8 — 0.65 0.76 9 1,2-propane diol 0.63 1.27 10 1,2-butane diol0.86 0.70 11 1,2-pentane diol 0.82 1.31 12 1,2-hexane diol 3.06 1.76 131,2-octane diol >6.16 >6.21 14 1,2-decane diol >6.28 >6.34

Examples 15-18 contained a wipe composition and a wipe substrate. Thewipe compositions are as shown in the table below. Examples 15-18 weretested as described above for Examples 5-7. Results are reported in thetable below. Surprisingly, it can be seen that only those compositionscontaining a 1,2-alkane diol have increased efficacy at wash 10.

TABLE 6 log₁₀ log₁₀ EXAM- REDUCTION REDUCTION PLE COMPOSITION WASH 1WASH 10 15 70 wt. % ethanol on SMS 3.05 2.09 substrate, untreated 16 70wt. % ethanol + 0.5 wt. % 3.86 4.44 1,2-octanediol on SMS substrate,untreated 17 80 wt. % ethanol on SMS 3.37 2.03 substrate, untreated 180.1 wt. % benzalkonium chloride 2.22 0.91 in water on SMS substrate,untreated

Examples 19-22 contain varying amounts of 1,2-octanediol in water, assummarized in the table below. In vitro efficacy of these compositionswas measured against E. coli, S. aureus, E. faecium, S. marcescens, S.aureus (MRSA), P. mirabilis, K. pneumoniae, and S. epidermidis. The testwas conducted according to the ASTM E 2315 method, “Standard Guide forAssessment of Antimicrobial Activity Using a Time-Kill Procedure.”Contact time was 15 seconds. Results are summarized in the table below.

TABLE 7 WT. % S. Klebsiella S. Candida Candida S. aureus S. DIOL (IN E.coli Marcenscens pneumoniae aureus tropicals albicans (MRSA) epidermisEXAMPLE WATER) 11229 14756 13883 6538 13803 14053 33591 12228 19 13.6 >5.3 nt 0.8 2.3 0.6 0.7 0.5 20 0.5 0.0 0.2 0.0 0.0 0.0 0.0 −0.2 0.121 0.25 −0.2 0.2 −0.1 0.1 0.0 0.0 −0.2 −0.1 22 0.125 0.0 0.0 0.1 0.0 ntnt nt nt

Examples 23-25 contain varying amounts of ethanol and 1,2-octanediol, assummarized in the tables below. In vitro efficacy of these compositionswas measured against S. marcescen, and S. aureus. The test was conductedaccording to the ASTM E 2315 method, “Standard Guide for Assessment ofAntimicrobial Activity Using a Time-Kill Procedure.” Contact time was 15seconds. Results are summarized in the tables below.

TABLE 8 Log Reduction—S. marcescens #14756 Wt. % ETHANOL Wt. % DIOL 0 1530 1.0 3.5 2.3 >5.1 0.5 0.3 0.1 >5.1 0 nt nt 0.45

TABLE 9 Log Reduction—S. aureus #6538 Wt. % ETHANOL Wt. % DIOL 0 15 301.0 0.2 2.6 0.9 0.5 0 0.2 0.1 0 nt nt 0

Thus, it should be evident that the invention herein is advantageous forseveral reasons including that additional antimicrobial compounds arenot needed in the formulations to pass the required healthcare personnelhand wash scrub test. This is advantageous because additionalantimicrobial agents can be irritating or even sensitizing to the skin,they add undue cost and manufacturing time to the formulations, and manyhave regulatory limitations preventing commercial sale worldwide. In oneor more embodiments, the antimicrobial composition of the presentinvention provides a 3 log reduction or greater against gram positiveand gram negative bacteria each time the product is used as directed.

Advantageously, the rapid efficacy of the compositions of the presentinvention provides adequate log reduction when less product is used thanwith conventional compositions. When less product can be used, a shorteramount of time is required for the product to be applied to the skin anddried. Thus, the time required for effective hand wash is reduced.

Furthermore, in one or more embodiments, the compositions of the presentinvention provide sustained or persistent protection. The compositionsexhibit moisturizing properties, and dispenser clogging and mis-directedoutput is reduced.

In one or more embodiments, the antimicrobial composition of thisinvention provides good product stability over a long-term shelf life.In certain embodiments, the stability of the antimicrobial compositionsof the present invention is better than the stability of products thatare emulsions or solid suspensions. Product stability includes physicalproperties such as stable viscosity and pH readings over time. Also,product stability requires that the products retain a uniformconsistency and appearance, and color and odor must not significantlychange so that aged product is different from freshly manufacturedproduct. In one or more embodiments, the antimicrobial compositions ofthe present invention exhibit good product stability over a shelf-lifeof about three years.

Various modifications and alterations that do not depart from the scopeand spirit of this invention will become apparent to those skilled inthe art. This invention is not to be duly limited to the illustrativeembodiments set forth herein.

1-40. (canceled)
 41. A foamable antimicrobial composition comprising: atleast 50 wt. % of a single antimicrobial agent consisting of one or moreC₁₋₆ alcohols, based upon the total weight of the antimicrobialcomposition; from about 0.02 to about 10 wt. % of a C₆₋₁₀ alkane diol,based upon the total weight of the antimicrobial composition; and afoaming surfactant selected from the group consisting of siloxanepolymer surfactants, fluorosurfactants, and mixtures thereof.
 42. Thefoamable antimicrobial composition of claim 41, wherein said C₁₋₆alcohol comprises one or more of ethanol, propanol, butanol, methanol,pentanol, hexanol, and isomers thereof.
 43. The foamable antimicrobialcomposition of claim 41, wherein said single antimicrobial agent ispresent in an amount of at least 65 wt. %.
 44. The foamableantimicrobial composition of claim 41, wherein the diol comprises1,2-hexanediol, 1,2-octanediol, 1,9-nonanediol, 1,2-decanediol,1,10-decanediol, or a mixture thereof.
 45. The foamable antimicrobialcomposition of claim 41, wherein the diol comprises a C₆₋₈ alkane diolor mixture thereof.
 46. The foamable antimicrobial composition of claim41, wherein the diol is present in an amount of at least about 0.05 wt.%, based upon the total weight of the antimicrobial composition.
 47. Thefoamable antimicrobial composition of claim 41, wherein the diol ispresent in an amount of from about 0.2 to about 0.75 wt. %, based uponthe total weight of the antimicrobial composition.
 48. The foamableantimicrobial composition of claim 41, comprising from about 0.002 toabout 4 wt. % of a siloxane polymer surfactant, based upon the totalweight of the antimicrobial composition.
 49. The foamable antimicrobialcomposition of claim 41, wherein said siloxane surfactant comprises oneor more of organopolysiloxane dimethicone polyols, silicone carbinolfluids, silicone polyethers, alkylmethyl siloxanes, amodimethicones,trisiloxane ethoxylates, dimethiconols, quaternized siliconesurfactants, polysilicones, silicone crosspolymers, and silicone waxes.50. The foamable antimicrobial composition of claim 41, wherein thefluorosurfactant comprises perfluoroalkylethyl phosphates,perfluoroalkylethyl betaines, fluoroaliphatic amine oxides,fluoroaliphatic sodium sulfosuccinates, fluoroaliphatic stearate esters,fluoroaliphatic phosphate esters, fluoroaliphatic quaternaries,fluoroaliphatic polyoxyethylenes, and mixtures thereof.
 51. The foamableantimicrobial composition of claim 41, wherein said foaming surfactantis present in said composition in at least about 0.01 wt. %, based uponthe total weight of the antimicrobial composition.
 52. The foamableantimicrobial composition of claim 41, wherein said composition furthercomprises 0.1 to 20 wt. % of one or more humectants, based upon thetotal weight of the antimicrobial composition.
 53. The foamableantimicrobial composition of claim 52, wherein said humectant includesone or more of propylene glycol, dipropyleneglycol, hexylene glycol,1,4-dihydroxyhexane, 1,2,6-hexanetriol, sorbitol, butylene glycol,propanediol s, dipropylene glycol, triethylene glycol, glycerin(glycerol), polyethylene glycols, ethoxydiglycol, polyethylene sorbitol,glycolic acid, glycolate salt, lactate salt, lactic acid, sodiumpyrrolidone carboxylic acid, hyaluronic acid, chitin, and mixturesthereof.
 54. The foamable antimicrobial composition of claim 41, whereinsaid composition includes less than 0.1 wt. % of preservative agents,based upon the total weight of the antimicrobial composition.
 55. Afoamable antimicrobial composition comprising: at least 50 wt. % of anantimicrobial agent comprising one or more C₁₋₆ alcohols, based upon thetotal weight of the antimicrobial composition; a C₆₋₁₀ alkane diol,wherein said C₆₋₁₀ alkane diol is present in an amount less than 1.0 wt.%, based upon the total weight of the antimicrobial composition.